Synthesis, characterization and nociceptive screening of new VV-hemorphin-5 analogues

Todorov, Petаr; Peneva, Petia; Pechlivanova, Daniela; Georgieva, Stela; Dzhambazova, Elena

doi:10.1016/j.bmcl.2018.07.040

Cited by 23 publications

(19 citation statements)

References 33 publications

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Section: Resultssupporting

confidence: 53%

“…This work is a continuation of our previous study on the synthesis and nociceptive effects of some new VV‐Hemorphin‐5 analogues (Todorov et al, ). The peptides V1–V7, presented in Table , have been prepared by SPPS‐Fmoc (9‐fluorenylmethoxycarbonyl) strategy (see Scheme ) according to the procedure described by us (Todorov et al, ). Based on Val‐Val‐Tyr‐Pro‐Trp‐Thr‐Gln‐NH 2 as a chemical template, we synthesized new C‐amide peptide derivatives of VV‐Hemorphin‐5 by replacement of Gln at position 7 with nonproteinogenic and/or natural amino acids (Val‐Val‐Tyr‐Pro‐Trp‐Thr‐ Aa1 ‐NH 2 ), where Aa1 is Lys/Orn/Dap/Dab.…”

Section: Resultssupporting

confidence: 53%

“…All of the VV‐Hemorphin‐5 analogues have been prepared by our recently described procedure (Todorov, Peneva, Pechlivanova, Georgieva, & Dzhambazova, ). RP‐HPLC and ESI‐MS data of all the compounds were identical to those previously described (Todorov et al, ). The synthesized peptides were checked by optical rotation and the analytical data are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

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Anticonvulsant evaluation and docking analysis of VV‐Hemorphin‐5 analogues

Todorov

Rangelov

Peneva

et al. 2019

Drug Development Research

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VV-Hemorphin-5 is an endogenous opioid peptide of the Hemorphin family with affinity at opioid receptors. A series of C-amide analogues have been synthesized, based on the structure of VV-Hemorphin-5, modified at position 1 and 7 by the un/natural amino acids (Aa8-Val-Val-Tyr-Pro-Trp-Thr-Gln-NH 2 and Val-Val-Tyr-Pro-Trp-Thr-Aa1-NH 2 ) using SPPS, Fmoc-chemistry. The peptide derivatives were evaluated for their anticonvulsant activity in three acute seizure tests in male ICR mice, the maximal electroshock (MES), the 6 Hz psychomotor seizure test, and the timed intravenous pentylenetetrazole (ivPTZ) infusion test.Their neurotoxicity was assessed in the rotarod test. Among the tested peptide analogues, V4 showed anticonvulsant activity in the three seizure tests that was comparable to the VV-Hemorphin-5 (V1) used as a positive control. While V5, V6, and V7 peptide derivatives exhibited anticonvulsant activity in the MES and 6 Hz test, they were inactive (V7) or showed pro-convulsant effect (V5 and V6) in the i.v. PTZ test. At a dose of 10 μg/mouse the peptide V2 was effective against clonic seizures induced by PTZ. Motor coordination was not affected by newly developed analogues of VV-Hemorphin-5. Docking study results suggest that kappa opioid receptor binding could be the mechanism of action of peptide derivatives with anticonvulsant activity. The results suggest that incorporation of nonproteinogenic and/or natural amino acids at position 1 and 7 of the VV-Hemorphin-5 scaffold deserve further evaluation in models of epilepsy and derivatization. K E Y W O R D Santiconvulsant activity, docking, Hemorphin analogues, mice, SPPS

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Section: Resultssupporting

confidence: 53%

Section: Resultssupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

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Anticonvulsant evaluation and docking analysis of VV‐Hemorphin‐5 analogues

Todorov

Rangelov

Peneva

et al. 2019

Drug Development Research

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“…However, as previous studies have proved, it is essential to consider a working-window analysis to differentiate azo-peptide related redox processes from those of secondary reactions on azobenzene-4,4'-dicarboxylic acid and VV-hemorphin-5and among other misleading interferences. The electrochemical study of Valorphine and Valorphine derivatives were previously reported by Todorov et al 2018 [5]. Anodic cyclic voltammogram for the oxidation of VV-hemorphin-5in phosphate buffer solution at Pt-electrode is shown in Fig.…”

Section: Resultsmentioning

confidence: 79%

Synthesis and characterization of new Hemorphin-5analogue containing azobenzene moiety with potential optical switching properties

Todorov¹,

Peneva²,

Georgieva-Kiskinova³

et al. 2018

Proceedings of the 35th European Peptide Symposium

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“…The series of hemorphin analogues have been synthesized and the structure-activity relationship of these compounds has been elucidated by Todorov's group [89]. The synthesis of peptides was performed manually using 9-fluorenylmethoxycarbonyl (Fmoc) solid phase synthesis.…”

Section: Hemorphin Analoguesmentioning

confidence: 99%

Hemorphins—From Discovery to Functions and Pharmacology

et al. 2021

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During the last three decades, a variety of different studies on bioactive peptides that are opioid receptor ligands, have been carried out, with regard to their isolation and identification, as well as their molecular functions in living organisms. Thus, in this review, we would like to summarize the present state-of-the art concerning hemorphins, methodological aspects of their identification, and their potential role as therapeutic agents. We have collected and discussed articles describing hemorphins, from their discovery up until now, thus presenting a very wide spectrum of their characteristic and applications. One of the major assets of the present paper is a combination of analytical and pharmacological aspects of peptides described by a team who participated in the initial research on hemorphins. This review is, in part, focused on the analysis of endogenous opioid peptides in biological samples using advanced techniques, description of the identification of synthetic/endogenous hemorphins, their involvement in pharmacology, learning, pain and other function. Finally, the part regarding hemorphin analogues and their synthesis, has been added.

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Synthesis, characterization and nociceptive screening of new VV-hemorphin-5 analogues

Cited by 23 publications

References 33 publications

Anticonvulsant evaluation and docking analysis of VV‐Hemorphin‐5 analogues

Anticonvulsant evaluation and docking analysis of VV‐Hemorphin‐5 analogues

Synthesis and characterization of new Hemorphin-5analogue containing azobenzene moiety with potential optical switching properties

Hemorphins—From Discovery to Functions and Pharmacology

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